A phase 3 study of celecoxib oral solution showed statistically significant improvements in the acute treatment of episodic migraine.
Richard Lipton, MD
Results of a phase 3 study of DFN-15 (celecoxib) demonstrate a significant treatment effect in acute episodic migraine versus placebo, with a generally favorable tolerability and safety profile.
The randomized, double-blind, placebo-controlled study included 622 patients (mean age, 40; 87% women) with a history of episodic migraine who were randomly assigned 1:1 to either 120 mg of DFN-15 or matching placebo containing 4/8 mL liquid, immediately following the onset of pain of moderate to severe intensity. The coprimary efficacy endpoints included the proportion of patients with freedom from pain and the absence of the most bothersome symptom (MBS) at 2 hours postdose.
Among the 622 patients included, 567 (91.2%) ultimately treated a migraine with a study drug (n = 285 DFN-15; n = 282 placebo). At 2 hours postdose, 35.6% of patients treated with DFN-15 were pain-free versus 21.7% of patients who received placebo (odds ratio [OR] 2.00, 95% CI, 1.36-2.94; P
<.001). In addition, treatment with DFN-15 was significantly superior versus placebo for freedom from the MBS (57.8% [134/232] vs 44.8% [104/232]; OR 1.68; 95% CI, 1.17-2.43; P
Of the 285 patients who received treatment with DFN-15, 13.3% reported a treatment-emergent adverse event (TEAE) compared with 8.9% of patients treated with placebo. Study drug-related TEAEs were reported in 9.1% (26/282) of patients administered DFN-15 compared with 6.0% (17/282) of patients in the placebo group. The most common study drug-related TEAEs were dysgeusia and nausea, reported in 4.2% and 3.2% of DFN-15-administered patients, respectively. Reported adverse events were mostly mild and common for the known safety and tolerability profile of celecoxib.
DFN-15 was also effective across multiple secondary endpoints, including pain relief, change in functional disability from baseline, relief of photophobia, 24-hour treatment satisfaction, use of rescue medication, and sustained pain relief and pain freedom. Patients did not experience any changes in vital signs or laboratory values.
The investigators pointed out that while both the liquid DFN-15 and 400 mg oral capsule formulations of celecoxib are effective for acute migraine, DFN-15 “produces higher peak plasma concentrations, is more rapidly absorbed, and has a shorter time to maximal concentration than celecoxib 400 mg oral capsules.”
“The faster time to maximum plasma concentration could translate into more rapid onset of pain relief, which is a treatment priority for people with migraine,” they wrote, noting that the “higher bioavailability could result in lower dose requirements and, in turn, greater GI [gastrointestinal] safety and tolerability.”
Lipton RB, Munjal S, Brand-Schieber E, Tepper SJ, Dodick DW. Efficacy, tolerability, and safety of DFN-15 (celecoxib oral solution, 25 mg/ml) in the acute treatment of episodic migraine: a randomized, double-blind, placebo-controlled study. Headache. Published online October 24, 2019. doi:10.1111/head.13663.